A clinical trial to see if a mesenchymal stem cells treatment called ORBCEL-C™ can help to treat primary sclerosing cholangitis, rheumatoid arthritis, lupus nephritis and Crohn’s disease
- Conditions
- Not ApplicablePrimary sclerosing cholangitis, rheumatoid arthritis, lupus nephritis, Crohn’s diseaseCholangitis, Rheumatoid arthritis, unspecified, Systemic lupus erythematosus with organ or system involvement, Crohn disease [regional enteritis]
- Registration Number
- ISRCTN80103507
- Lead Sponsor
- niversity of Birmingham
- Brief Summary
2022 Protocol article in https://pubmed.ncbi.nlm.nih.gov/36691123/ (added 24/01/2023) 2023 Other publications in https://doi.org/10.1186/s41687-023-00634-3 Development and usability testing of an electronic patient-reported outcome (ePRO) solution (added 10/10/2023)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 60
Current participant inclusion criteria as of 02/07/2024:
Inclusion criteria for ALL patients:
1. Age = 18 years at Visit 1/1a (screening)
2. In this clinical trial, for all cohorts, only participants with severe active disease and refractory to the standard of care treatment (and biologic-refractory for Rheumatoid Arthritis and Crohn’s Disease cohort) can be included (where a standard of care therapy is available*)
3. Active, uncontrolled, or partially controlled inflammatory disease despite receiving standard-of-care therapy (where a standard-of-care therapy is available*)
4. On an approved therapy if indicated and available, unless the patient is intolerant of, or has refused, the standard of care therapy
*For patients with PSC, no ‘standard of care treatment’ or standard definition for ‘uncontrolled/partially controlled disease’ is available. Patients must have severe active disease to be included.
Inclusion criteria specific to patients with primary sclerosing cholangitis (PSC):
1. Diagnosis of PSC at Visit 1a (screening) as evidenced clinically by Radiological AND/OR histological evidence. Individuals with small duct PSC may be included, only if they have concomitant inflammatory bowel disease
2. Serum ALP = 1.5 x ULN at Visit 1a and 1b (screening)
3. Serum ALP value at Visit 1b within ± 40% of ALP value at Visit 1a as per the formula below:
3.1. ((ALPVisit 1b - ALPVisit 1a) / ALPVisit 1a) x 100 = 40%
4. At Visit 1b, it should be confirmed that a patient does not meet any of the exclusion criteria
Inclusion criteria specific to patients with rheumatoid arthritis (RA):
1. Patients fulfilling 2010 ACR/EULAR criteria or 1987 ACR criteria for a diagnosis of RA for = 6 months
2. Previous failure (inefficacy according to investigator judgement) to at least one biologic therapy or targeted synthetic Disease-Modifying Anti-Rheumatic Drug (tsDMARD)
3. DAS28 ESR = 3.2 with at least three swollen joints
4. Willing to have a synovial biopsy
Inclusion criteria specific to patients with lupus nephritis (LN):
1. Has received induction of remission therapy for new diagnosis OR relapse of LN within 36 months of Visit 1 (screening) with corticosteroids AND mycophenolate mofetil OR azathioprine OR cyclophosphamide OR rituximab
2. Renal biopsy with evidence of active LN within 36 months of Visit 1 (screening). Biopsy-proven active LN for the purposes of eligibility is defined as LN class III, IV or V with evidence of activity. Concurrent evidence of chronic damage is permitted (Priority will be given to the recruitment of patients with biopsy-proven evidence of active LN within 36 months of the screening date. Patients that have had a renal biopsy with evidence of active lupus nephritis prior to 36 months of Visit 1 [screening] may be recruited following discussion with the coordinating centre as long as they have received induction of remission therapy within 36 months of Visit 1 [screening], as per inclusion criterion 1)
3. Ongoing proteinuria with uACR = 50 mg/mmol
4. If the patient is on mycophenolate mofetil or azathioprine, stable or reducing dose of the drug for the last three months prior to Visit 1 (screening)
Main inclusion criteria specific to patients with Crohn’s disease (CD):
1. Confirmed diagnosis of CD as per standard clinical criteria
2. Colonoscopic detection of post-operative disease recurrence as scored as Rutgeerts > i2a (i2b, i3 or i4) OR Active Crohn’s disease with SES-CD = 7 with at least one area of stricturing < 5cm in l
Current participant exclusion criteria as of 02/07/2024:
Exclusion criteria for ALL patients
1. Refusal or lacks the capacity to give informed consent to participate in the POLARISE Trial
2. Patient who is unable to participate in follow-up assessment
3. Participation actively or within five half-lives of Investigational Medicinal Product (IMP) and/or Advanced Therapy Investigational Medicinal Product (ATIMP) in another clinical trial
4. Known hypersensitivity to the ATIMP
5. Evidence of active malignancy (within three years of Visit 1/1a [screening]), other than non-melanoma skin cancer and cervical dysplasia in situ
6. Major surgical procedure within 30 days of Visit 1/1a (screening)
7. Prior organ transplantation (with the exception of a corneal transplant = three months prior to Visit 1/1a [screening])
8. Active harmful alcohol consumption as evaluated and documented by the Investigator (as defined by NICE [3])
9. Any active treatment on biologic therapy (monoclonal antibodies), or within the washout period for previous biologic therapy at the time of screening (Visit 1/1a)
10. Received oral corticosteroids > 10 mg (prednisolone or equivalent) in the four weeks prior to Visit 2 (first ORBCEL-C™ administration)
11. Clinically severe cardiovascular disease as evaluated by the Investigator
12. Pregnancy or breast-feeding
13. Women of childbearing potential (see Appendix 1 for definition) who are unwilling to practise effective contraception (see Appendix 2 for further detail) for the duration of the trial and up to 90 days after the last trial drug is administered. If using hormonal agents the same method must have been used for at least one month before the trial dosing and patients must use a barrier method during that time period
14. Non-vasectomised men, sexually active with women of childbearing potential, who are not willing to practise effective contraception (i.e. condom with spermicide) for the duration of the trial and up to 90 days after the last trial drug is administered
15. Any evidence of current (surface antigen positive) hepatitis B infection
16. Patients with active hepatitis C infection (Polymerase Chain Reaction (PCR) positive)
17. Known positivity for antibody to HIV
18. Presence of an acute/chronic infection or illness that, at the discretion of the Investigator, might compromise the patient’s health and safety in the trial
19. Receipt of live vaccination within six weeks prior to Visit 1/1a (screening)
20. Any symptoms indicative of COVID-19
21. Renal impairment defined as an eGFR < 30ml/min at Visit 1/1a (screening).
22. Confirmed or clinically suspected liver cirrhosis
Exclusion criteria specific to patients with primary sclerosing cholangitis:
1. Documented alternative aetiology for sclerosing cholangitis (i.e. secondary sclerosing cholangitis)
2. A dominant (as determined by the Investigator) alternative chronic or active liver injury other than PSC at the time of Visit 1a (screening)
3. Ursodeoxycholic Acid (UDCA) dose modification within the last 90 days
4. ALP > 10 x ULN at Visit 1a (screening)
5. Evidence of cholangitis within 90 days of Visit 1a (screening), i.e. documented evidence of cholangitis by a doctor
6. Need for any systemic antibiotics (oral or intravenous) within 90 days of Visit 1a (screening)
7. Any patient taking new prophylactic antibiotics for recurrent cholangitis started or dosage changed in the last 90 days
8. Presence of percutaneous biliary drain or internal biliary stent
9. Diagnos
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Current primary outcome measure as of 02/07/2024:<br>The relative proportion of M1- and M2-like monocyte/macrophage cells in peripheral blood, determined from cell counts quantified using flow cytometry, after ORBCEL-C™ administration:<br>PSC patients: at Visits 2, 3, 4, 5, 6 & 7<br>RA patients: at Visits 2, 3, 4, 5, 6 & 7<br>LN patients: at Visits 2, 3, 4, 5, 6, 7 & 8<br>CD patients: at Visits 2, 3, 4, 5, 6, 7 & 8<br><br><br><br><br>Previous primary outcome measure:<br>The relative proportion of M1- and M2-like monocyte/macrophage cells in peripheral blood, determined from cell counts quantified using flow cytometry, after ORBCEL-C™ administration:<br>PSC patients: at Visits 2, 3, 4, 5, 6 & 7<br>RA patients: at Visits 2, 3, 4, 5, 6 & 7<br>LN patients: at Visits 2, 3, 4, 5, 6, 7 & 8<br>CD patients: at Visits 2, 3, 4, 5, 6, 7 & 8a
- Secondary Outcome Measures
Name Time Method